tbuckley/cabot-search huggingface dataset:
Patterns of venous thromboembolism risk, treatment, and outcomes among patients with cancer from uninsured and vulnerable populations
Authors: Wilson L. da Costa, Danielle Guffey, Abiodun Oluyomi, Raka Bandyo, Omar Rosales, Courtney D. Wallace, Carolina Granada, Nimrah Riaz, Margaret Fitzgerald, David A. Garcia, Marc Carrier, Christopher I. Amos, Christopher R. Flowers, Ang Li
Journal: American Journal of Hematology (2022)

Abstract The epidemiology of cancer‐associated thrombosis (CAT) among uninsured and vulnerable populations in the US is not well‐characterized. We performed a retrospective cohort study for patients with newly diagnosed cancer from 2011 to 2020 at Harris Health System, which cares for uninsured residents in the Houston metropolitan area. Patient demographics, NCI comorbidity index, area of deprivation index (ADI), cancer histology, staging, and systemic therapy data were extracted. CAT included overall venous thromboembolism (VTE) or pulmonary embolism +/− lower extremity deep vein thrombosis (PE/LE‐DVT) within 1 year of diagnosis. We used multivariable Fine‐Gray models to assess the associations with CAT accounting for death as a competing risk. Among 15 342 patients, 74% were uninsured and 84% lived in socioeconomically disadvantaged neighborhoods. There were 16% Non‐Hispanic White (NHW), 28% Non‐Hispanic Black (NHB), 50% Hispanic (27% Mexican), and 6% Asian/Pacific Islanders (API). The 1‐year CAT incidence rate was 14.6%. Overall VTE was lower for Hispanics versus NHW (SHR 0.87 [0.76–0.99]) and API versus NHW (SHR 0.58 [0.44–0.77]). PE/LE‐DVT was higher for NHB versus NHW (SHR 1.18 [1.01–1.39]). CAT was also associated with chemotherapy‐based regimens (+/− immunotherapy), age, obesity, cancer type/staging, VTE history, and recent hospitalization. NCI comorbidity and ADI scores were associated with mortality but not CAT. In a large cohort of underserved patients with cancer, we identified an elevated incidence of CAT with known and novel risk predictors. Hispanics had lower adjusted rates of CAT and mortality. Our findings highlight the need to investigate and incorporate vulnerable populations in clinical trials.
GCT-09. Transcriptome and methylome profiles of CNS germ cell tumors and their comparison with testicular counterpart
Authors: Hirokazu Takami, Asmaa Elzawahry, Yasin Mamatjan, Mamoru Kato, Natsuko Hama, Tatsuhiro Shibata, Yoichi Nakazato, Ryo Nishikawa, Masao Matsutani, Koichi Ichimura
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: The pathophysiology of CNS germ cell tumors (GCTs) has yet to be fully unraveled, resulting in the paucity of treatment options. The biological comparison with its testicular counterpart has not been interrogated. METHODS: In total, 84 cases of CNS GCT were investigated for methylation and transcriptome analyses, and an integrative analysis of the normal cells undergoing embryogenesis and testicular GCTs was conducted. RESULTS: Transcriptome analysis revealed germinoma and non-germinomatous GCTs (NGGCTs) were clearly separated. On transcriptome, germinoma was characterized by primitive cell state, closely related to primordial germ cell (PGC) with meiosis/mitosis potentials. NGGCT had a feature of more differentiated cell state directed toward organogenesis. Germinoma was subdivided into two clusters on integrated transcriptome and methylation analysis, and they are different in the age distribution and tumor cell content. CNS and testicular GCTs were divided based on histology, either germinoma/seminoma or NGGCT/non-seminomatous GCTs on methylation. Expression analysis mainly clustered them depending on the site of origin and histology. CONCLUSIONS: Expression profiles of CNS GCTs distinctly reflect the histological variabilities. Germinoma may be clustered into two groups, with possible differentiation in treatment intensity in the future. GCTs at CNS and gonads seem to have a mutual cell-of-origin and similar genomic backgrounds, which potentiates site-agnostic treatment development.
PATH-15. Molecular and clinical landscape of CNS tumors arising among adolescents and young adults (AYA) at Memorial Sloan Kettering Cancer Center (MSKCC): a single-institutional experience
Authors: Bryan K Li, Alexandra Miller, Nancy Bouvier, Katherine Hill, Michael F Berger, Sameer Farouk Sait, Matthias Karajannis
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: The management of CNS tumors arising among AYA represents an unmet challenge. Treatment may be split between pediatric and adult centers, often with conflicting approaches. Biology also appears to be distinct compared to younger/older age groups but has yet to be fully characterized. Such features would have important implications for prognostication and informing vulnerabilities for targeted therapies.METHODS: To establish the clinical and molecular landscape of these tumors, we analyzed all cases in patients aged 15-39 years old who were treated at MSKCC between 2018-2021. RESULTS: 302 patients with accompanying MSK-IMPACT targeted sequencing, copy number analysis, Archer fusion panel, and clinical data were found. 239/302 cases (79%) were gliomas, with the remaining consisting mainly of neuro-epithelial tumors (n=15; 5%), meningiomas (9; 3%), ependymomas (10; 3%), and embryonal tumors (7; 2%). Among gliomas, 163/239 (68%) had IDH1/2 mutations, which were significantly more enriched for TP53 (121/163; 74%) and ATRX (90/163; 55%) co-mutations compared to IDH-wild type (IDH-WT) (q&amp;lt;0.0001). In comparison, IDH-WT gliomas (n=76) were enriched for alterations in BRAF (16/76 with SNV, 9/76 fusion; q&amp;lt;0.0001), H3F3A (14/76; q&amp;lt;0.0001), PTEN (10/76; q=0.038), and CDKN2A (16/76; q=0.038). Among 113 patients with high-grade gliomas (WHO grade 3/4), those with IDH-WT tumors (n=34) had a poorer prognosis that those with IDH-mutant tumors (n=79) (1 and 5-year OS of 68% and 28% vs. 97% and 76%, respectively) (p&amp;lt;0.0001). Further, a lower frequency of alterations in TERT (26/113; 23%), EGFR (6/113; 5%), and PDGFRA (4/113; 4%) were observed compared to previous studies for adult-only cohorts (~50-70%, 40%, and 10%, respectively). CONCLUSIONS: IDH-mutant gliomas were the most common tumor type seen in this AYA cohort. However, some alterations characteristic of adult high-grade gliomas (TERT, EGFR, PDGFRA) were not as frequently observed. Additional identification of molecular features that predict response to conventional and targeted therapies is underway.
Impact of trial site selection on minority patient recruitment in prostate cancer trials.
Authors: Charles Lagor, Sudip Bhandari, Jitesh Chawla, Margot Knight, Jeremy Mann, Judith Mueller, Paola Raska, Steve Southwick, Warren Whyte
Journal: Journal of Clinical Oncology (2022)

1558 Background: Historically, minority patients have been underrepresented in clinical cancer trials. Despite recognition of this problem, trials in the early 2000’s showed a decrease from 10.5% to 6.2% in African American trial participation when compared to trials from the early 1990’s. The drop in trial participation is also reflected in prostate cancer trials, although Black men have a 1.76 higher prostate cancer incidence rate than White men. Using prostate cancer as an example, we investigated the impact of trial site selection on potential minority patient recruitment; thus, overcoming a major system-level barrier to trial access. Methods: We created a prostate cancer cohort by filtering our real-world data sources (CancerLinQ, Electronic Medical Office Logistics) for adult male patients with ICD10 CM code C61* or ICD9 CM code 185 on 1/1/2015 or later (cohort #1). As a pre-requisite for computing site level prostate cancer patient counts, we used claims data to attribute missing site information. Finally, to identify the most promising sites for minority trial recruitment, we ranked sites by the proportion of Black patients and the overall cohort patient count. We repeated the above steps for a subset of cohort #1, which was based on the criteria for trial NCT00887198 investigating the prostate cancer drug abiraterone (cohort #2). Results: The prostate cancer cohort (#1) had 151,261 patients, of which 99,152 (65.6%) were attributed to sites. The percentage of Black patients being treated at the top ten sites ranged from 33.0% to 66.4%, with a median of 45.2% (see table). All ten sites had participated in an interventional cancer trial, and eight had participated in prostate cancer trials. Half of them were community, and half were academic sites. The abiraterone cohort (#2) had 1,267 patients, of which 1,174 (92.7%) were attributed to sites. Among the top ten sites the Black patient percentages ranged from 23.8% to 85.7%, with a median of 39.3%. Conclusions: In an analysis of 17 recent FDA drug registration trials for prostate cancer, Black trial participation ranged from only 1.4% to 6.2%, with a median of 3.0%. In contrast, Black patients being treated at the top sites in our data ranged from 33.0% to 66.4%, with a median of 45.2% (cohort #1). The percentages for the abiraterone cohort (#2) were similar, suggesting that even after applying trial criteria the Black patient percentages remain in the double-digits at top sites. Our results demonstrate that informed trial site selection could have a substantial positive impact on minority patient recruitment. [Table: see text]
Soybean extracts (glycine max) associated with curcuma, boswellia, pinus and urtica (PROSTAFLOG®) are able to improve quality of life in patients affected by CP/CPPS: Is the pro-inflammatory cytokine IL-8 decreasing the physiopathological link?
Authors: T. Cai, I. Tamanini, P. Verze, A. Palmieri
Journal: European Urology (2022)
Neoadjuvant HER2-targeted therapy +/- immunotherapy with pembrolizumab (neoHIP): An open-label randomized phase II trial.
Authors: Heather L. McArthur, Jorge Henrique S. Leal, David B. Page, Christina DiLauro Abaya, Reva K Basho, Michelle Phillips, David Chan, Hugo Hool, Dorothy J. Park, Mary El-Masry, Philomena McAndrew, Swati Sikaria, Laura Spring, Aditya Bardia, Mourad Tighiouart, Farnaz Dadmanesh, Armando E. Giuliano, Stephen Lawrence Shiao
Journal: Journal of Clinical Oncology (2022)

TPS624 Background: Immune checkpoint inhibition (ICI) is synergistic with HER2-directed therapy in pre-clinical models. Clinically, pembrolizumab (K)-mediated ICI plus HER2-directed therapy with trastuzumab (H) was safe and demonstrated modest activity in H-resistant HER2-positive (HER2+) metastatic breast cancer. Because ICI may confer more robust activity when administered earlier in the course of disease, H and K administered in the curative-intent, treatment-naive setting may allow for de-escalation of cytotoxics; confer life-long, tumor-specific immunity; and ultimately, improve cure rates. Moreover, the synergy of H and K with paclitaxel (T) may overcome the need for dual HER2-blockade with H plus pertuzumab (P). In this randomized, multicenter, phase II, open-label trial the efficacy and safety of neoadjuvant THP vs THP-K vs TH-K are explored. Methods: 174 patients (pts) ≥18y with previously untreated, stage II-III, HER2+ breast cancer will be randomized and stratified by clinical nodal status (positive vs. negative) and hormone receptor status (positive vs. negative). In arm A, pts receive T at 80mg/m2 weekly for 12 weeks, H at 8mg/Kg (loading dose) and then 6mg/Kg every 3 weeks x 3 doses, P at 840 mg (loading dose) and then 420mg/Kg every 3 weeks x 3 doses (THP). In arm B, pts receive THP plus K at 200mg every 3 weeks x 4 doses (THP-K). In arm C, pts receive TH-K. Definitive surgery is 3-6 weeks after the last dose. After surgery, pts are treated per the treating physician’s discretion including radiotherapy per local clinical standard. Pts whose tumors are hormone-receptor positive will receive hormone therapy per local standard-of-care. The primary end point is pathologic complete response (pCR) rate in the breast and axilla (ypT0/Tis ypN0). Secondary end points include pCR rate by ypT0ypN0 and ypT0/Tis, residual cancer burden index, event free survival, breast conserving surgery rate, safety and overall survival. Exploratory correlative studies will characterize potential immune biomarkers predictive of efficacy and/or toxicity. Clinical trial information: NCT03747120.
Association of Leucocyte levels in urine with tissue PD-L1 status and immune infiltration into basal bladder cancer subtype in the prospective Real World clinicopathological register trial BRIDGister
Authors: R. Wirtz, F. Friedersdorff, E. Veltrup, D. Barski, R. Bug, T. Otto, E. Kilic, R. Hake, S. Eidt, J. Roggisch, S. Koch, T.H. Ecke
Journal: European Urology (2022)
Proof-of-concept study to improve risk prediction after anterior urethroplasty by prospective intraoperative assessment of anatomico-morphological stricture features
Authors: M.W. Vetterlein, O. Engel, L. Kühnke, F. König, L. Ding, B. Kranzbühler, A. Soave, R. Dahlem, M. Fisch, P. Marks
Journal: European Urology (2022)
Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolism
Authors: F. Chen, W. A. M. Elgaher, M. Winterhoff, K. Büssow, F. H. Waqas, E. Graner, Y. Pires-Afonso, L. Casares Perez, L. de la Vega, N. Sahini, L. Czichon, W. Zobl, T. Zillinger, M. Shehata, S. Pleschka, H. Bähre, C. Falk, A. Michelucci, S. Schuchardt, W. Blankenfeldt, A. K. H. Hirsch, F. Pessler
Journal: Nature Metabolism (2022)

Although the immunomodulatory and cytoprotective properties of itaconate have been studied extensively, it is not known whether its naturally occurring isomers mesaconate and citraconate have similar properties. Here, we show that itaconate is partially converted to mesaconate intracellularly and that mesaconate accumulation in macrophage activation depends on prior itaconate synthesis. When added to human cells in supraphysiological concentrations, all three isomers reduce lactate levels, whereas itaconate is the strongest succinate dehydrogenase (SDH) inhibitor. In cells infected with influenza A virus (IAV), all three isomers profoundly alter amino acid metabolism, modulate cytokine/chemokine release and reduce interferon signalling, oxidative stress and the release of viral particles. Of the three isomers, citraconate is the strongest electrophile and nuclear factor-erythroid 2-related factor 2 (NRF2) agonist. Only citraconate inhibits catalysis of itaconate by cis-aconitate decarboxylase (ACOD1), probably by competitive binding to the substrate-binding site. These results reveal mesaconate and citraconate as immunomodulatory, anti-oxidative and antiviral compounds, and citraconate as the first naturally occurring ACOD1 inhibitor.
Frailty status derived from the electronic medical record to predict survival and health care utilization in veterans with lung and gastrointestinal cancers.
Authors: Sudha Yarlagadda, Javad Razjouyan, Aanand Naik, Yvonne Sada
Journal: Journal of Clinical Oncology (2022)

6582 Background: Frailty is associated with increased vulnerability to stressors. Although frailty is a predictor of survival, traditional frailty assessments are not feasible in clinical practice. Frailty indexes (FI) derived from the electronic medical record (EMR) are an alternate approach. There is limited data for the association between EMR-FI and cancer-related outcomes including survival and health care utilization. Methods: We identified a cohort of patients diagnosed with lung or gastrointestinal cancer from 2016-2020 using VA administrative files. We used the Veterans Affairs-FI (VA-FI), a validated 31-item cumulative deficit FI, to define three groups: robust (≤0.1), prefrail (0.1-0.2), frail ( &gt; 0.2). Cox proportional hazard analyses were conducted to evaluate survival. Logistic regression analyses were performed to examine healthcare utilization. All models were adjusted for age, gender, race, Charlson comorbidity index, and stage. Results: Among 37,439 patients (age: 70±8.6 years), the majority were prefrail (36.8%) or frail (24.1%). Prefrail patients had a 13% increased risk of death compared to robust patients (adjusted hazard ratio [aHR] 1.13; 95% CI 1.10-1.16), while frail patients had a 52% increased risk (aHR 1.52; 95% CI 1.47, 1.57). Pre-frail and frail patients had increased odds of 1-year ED visits (adjusted odds ratio [aOR] 1.33; 95% CI 1.27 - 1.40 and aOR, 1.88, 95% CI 1.77-2.00, respectively). Frailty status was associated with increased odds of 1-year all-cause hospitalization among prefrail (aOR 1.09; 95% CI 1.03-1.15) and frail patients (aOR 1.26; 95%CI: 1.18, 1.34). Conclusions: Frailty measured by EMR data is significantly associated with survival and healthcare utilization among patients with lung and gastrointestinal cancers, independent of stage. Further study is warranted to develop EMR-FI as a risk stratification tool for personalized cancer treatment decisions.
The beneficial effects of alpha-blockers, antimuscarinics, beta 3-agonist and PDE5-inhibitors for ureteral stent-related discomfort: A systematic review and meta-analysis from KSER update series
Authors: S-W. Lee, D.Y. Chung, M.H. Lee, D.K. Kim, H.D. Jung, S. Paick, S.H. Jeon, J.Y. Lee
Journal: European Urology (2022)
TBIO-10. NGS molecular profile of paediatric brain tumours: results from 92 consecutive patients treated at Centro Hospitalar Universitário de São João
Authors: Jorge Lima, Jorge Pinheiro, Susana Nunes, Ana Paula Fernandes, Paula Soares, Jose Carlos Machado, Josue Pereira, Maria Joao Gil da Costa
Journal: Neuro-Oncology (2022)

Abstract AIM: Our aim was to progress in bringing molecular medicine to routine clinical practice in the setting of paediatric neuro-oncology. We have implemented a protocol between Ipatimup and Centro Hospitalar Universitário de São João for the rapid and efficient delivery of the molecular portrait of paediatric brain tumours. MATERIAL AND METHODS: We have enrolled 92 patients with the following inclusion criteria: Age 0-18 years; newly diagnosed brain tumour; previously diagnosed brain tumour, whenever it presented as rare, aggressive or refractory disease; availability of tumour material; signed informed consent. Tumour samples were centrally reviewed by expert pathologists and profiled using the Oncomine Childhood Cancer Research Assay. RESULTS: In the 92 tumours that were molecularly profiled, BRAF was the most frequently altered gene, especially in pilocytic astrocytomas, being also detected in other LGG and HGG. Other commonly mutated genes were PIK3CA and FGFR, the former in HGG and the latter in LGG. MYB and RAF1 rearrangements were also found in low grade glial/glioneuronal tumours, while HGG showed a more complex profile, with many cases harbouring multiple alterations in EGFR, PDGFRA, ATRX, H3F3A, HIST1H3B, TP53, among others. A 16-year old patient with CMMR (homozygous mutation in PMS2) developed a glioblastoma that carried nearly 5x the average number of mutations. Among the 8 medulloblastomas, 2 showed mutations in the SHH pathway (1 in PTCH1 and one in SUFU) and 2 in the WNT pathway (1 in CTNNB1 and one in APC). In the remaining cases, one ependymoma presented MYCN amplification, while no alterations were detected in 3 patients. CONCLUSIONS: This study enabled the detailed molecular study of 92 paediatric brain patients, allowing a more robust tumour classification and the identification of actionable alterations. A subset of the patients are already undergoing targeted therapy, mainly using BRAF or MEK inhibitors with generally good improvement.
Cost per Event Averted in Cancer Trials in the Adjuvant Setting From 2018 to 2022
Authors: Idine Mousavi, Timothée Olivier, Vinay Prasad
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Adjuvant therapies are often approved based on improvements in disease-, progression-, or relapse-free survival (ie, an event). An important estimate in adjuvant therapies is the cost per event averted. <h3>Objective</h3> To characterize the costs per event averted of anticancer drugs approved by the US Food and Drug Administration (FDA) between January 2018 and March 2022. <h3>Design, Setting, and Participants</h3> In this cross-sectional study, all approvals were reviewed from the FDA website. Approvals selected for the analysis needed to be drawn from randomized trials involving anticancer drugs studied in the adjuvant treatment of solid tumors. Treatments of nonsolid tumors; nonrandomized, noncontrolled trials; and unpublished trials were excluded. Approvals between January 2018 and March 2022 were included, and 11 trials met inclusion criteria. The monthly costs of each agent were abstracted from the Micromedex RED BOOK database. All variables included in calculations were derived from the original trial publication. Information abstracted for each approval included the name of the drug approved, name of the trial, primary end point, dosing regimen in the trial, median duration of treatment, tumor type, monthly costs per drug, and the number needed to treat for the primary end point. Data were analyzed in March 2022. <h3>Main Outcomes and Measures</h3> The cost per event averted for each agent studied in each clinical trial; the monthly cost of each drug, the cost per patient for each drug, the primary clinical end point studied in each trial; the study's design and setting. <h3>Results</h3> A total of 11 approvals were included in the study. From January 2018 to March 2022, all approvals were based on a surrogate end point as the primary end point, with no trials demonstrating, to date, an overall survival benefit. The median cost per event averted of drugs in the adjuvant setting was $1 610 000 (range, $820 000 to $2 640 000). The median cost of a complete adjuvant treatment was $158 000 per patient. <h3>Conclusions and Relevance</h3> In this cross-sectional study, anticancer agents in the adjuvant setting were approved based on disease-, progression-, event-, or relapse-free survival. Costs per event averted were high. These findings suggest that these drugs may not achieve wide or global use unless their efficacy improves or their prices decrease.